Tablets containing a theophylline-glutaric acid (TG) cocrystal dissociated rapidly forming crystalline theophylline (20-30%), following storage at 40 °C/75% RH for 2 weeks. Control tablets of TG cocrystal containing no excipients were stable under the same conditions. The dissociation reaction was water-mediated, and the theophylline concentration (the dissociation product), monitored by synchrotron X-ray diffractometry, was strongly influenced by the formulation composition. Investigation of the binary compacts of the TG cocrystal with each excipient revealed the influence of excipient properties (hydrophilicity, ionizability) on cocrystal stability, providing mechanistic insights into a dissociation reaction. Ionizable excipients with a strong tendency to sorb water, for example, sodium starch glycolate and croscarmellose sodium, caused pronounced dissociation. Microcrystalline cellulose (MCC), while a neutral but hydrophilic excipient, also enabled solution-mediated cocrystal dissociation in intact tablets. Magnesium stearate, an ionizable but hydrophobic excipient, interacted with the cocrystal to form a hygroscopic product. The interaction is believed to be initiated in the disordered cocrystal-excipient particle interface. In contrast, the cocrystal was stable in the presence of lactose, a neutral excipient with no tendency to sorb water. The risk of unintended cocrystal dissociation can be mitigated by avoiding contact with water both during processing and storage.

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A series of copolymers based on acrylonitrile (AN) and acrylic acid (AA) with varying architecture and composition were synthesized using free radical polymerization. The distribution of monomers in the copolymer chains could be successfully controlled by regulating the addition of more reactive monomer (AA). Copolymers having nearly random distribution of comonomer moieties to block type distribution with different composition (10-50 mol % AA) were synthesized to investigate the effect of polymer architecture and composition on pH response and mechanical properties of resultant structures. These copolymers were solution spun from dimethylformamide-water system, drawn in coagulation bath, and annealed at 1208C for 2 h to make pH-sensitive fibers which were structurally stable without the need of chemical crosslinking. The fibers from block copolymers showed significantly better tensile strength (34.3 MPa), higher retractive forces (0.26 MPa), and enhanced pH response (swelling 3890%) in comparison with fibers from random copolymer (13.55 MPa, 0.058 MPa, and 1723%, respectively). The tensile strength and retractive forces could be further improved to a value of 72 MPa and 0.36 MPa, respectively, by changing the composition of the block copolymer while retaining the swelling percentage similar to the random copolymer mentioned above. It is proposed that on processing to fibers, the block copolymers could form a segregated domain structure with separate domains of AA and AN, where AN domains were responsible for high structural integrity by providing connectivity among polymer chains, while AA domains showed improved response to changing pH of the environment.